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Technology : Probe sheds light on the brain

By David Bradley

A MOLECULE that glows when it detects an important brain chemical could lead
to a new sensor for studying diseases such as Huntington’s disease, epilepsy and
Parkinson’s disease, according to researchers at Queen’s University,
Belfast.

Chemist Prasanna de Silva and his team have designed a molecule that grabs
hold of both ends of the nerve-signalling molecule gamma-aminobutyric acid
(GABA). GABA is one of a group of ions called zwitterions—they have a
positive charge at one end and a negative one at the other—which makes it
difficult to grab hold of both ends at the same time in order to get a signal
from a sensor molecule. Try to bind one end with, say, a positively charged
chemical group and the other will be repelled. But de Silva and his team have
now succeeded in building a molecular trap for GABA. Their molecule glows in
ultraviolet light when GABA is attached.

They engineered one end of the molecule so that it would attract a negative
charge, and added a spacer between that and the fluorescent portion. They
followed this with a second spacer, to which they attached a chemical group to
attract the positive end of GABA. The spacers keep the charges far enough apart
to allow GABA to get a grip.

De Silva speculates that the molecule might be built into a thin probe that
could be inserted into the brain and used to monitor GABA levels in response to
drugs or other stimulation. Low levels of GABA in the brain cause the
involuntary jerky movements associated with Huntington’s disease.

But de Silva knows more work must be done before a practical probe will be
possible. “The sensor molecule must sense GABA under physiological conditions,”
he says. His team reported its discovery in Chemical Communications
(1996, p 2191).